C. elegans HIM-17 links chromatin modification and competence for initiation of meiotic recombination

Cell. 2004 Aug 20;118(4):439-52. doi: 10.1016/j.cell.2004.07.026.

Abstract

Initiation of meiotic recombination by double-strand breaks (DSBs) must occur in a controlled fashion to avoid jeopardizing genome integrity. Here, we identify chromatin-associated protein HIM-17 as a link between chromatin state and DSB formation during C. elegans meiosis. Dependencies of several meiotic prophase events on HIM-17 parallel those seen for DSB-generating enzyme SPO-11: HIM-17 is essential for DSB formation but dispensable for homolog synapsis. Crossovers and chiasmata are eliminated in him-17 null mutants but are restored by artificially induced DSBs, indicating that all components required to convert DSBs into chiasmata are present. Unlike SPO-11, HIM-17 is also required for proper accumulation of histone H3 methylation at lysine 9 on meiotic prophase chromosomes. HIM-17 shares structural features with three proteins that interact genetically with LIN-35/Rb, a known component of chromatin-modifying complexes. Furthermore, DSB levels and incidence of chiasmata can be modulated by loss of LIN-35/Rb. These and other data suggest that chromatin state governs the timing of DSB competence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / physiology*
  • Chromatin / metabolism*
  • Chromosome Mapping
  • DNA Methylation
  • DNA-Binding Proteins / metabolism
  • Endodeoxyribonucleases
  • Esterases / metabolism
  • Green Fluorescent Proteins
  • Histones / metabolism
  • In Situ Hybridization, Fluorescence
  • Indoles
  • Karyotyping
  • Luminescent Proteins / metabolism
  • Lysine / chemistry
  • Meiosis*
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Prophase
  • Protein Structure, Tertiary
  • RNA Interference
  • Rad51 Recombinase
  • Recombination, Genetic*
  • Sequence Homology, Amino Acid
  • Time Factors

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • HIM-17 protein, C elegans
  • Histones
  • Indoles
  • Luminescent Proteins
  • Green Fluorescent Proteins
  • DAPI
  • Rad51 Recombinase
  • rad-51 protein, C elegans
  • Endodeoxyribonucleases
  • Esterases
  • meiotic recombination protein SPO11
  • Lysine